Destruction of leukemia cells in vivo in AKR mice resulting from infusion of blood, plasma or serum from normal animals requires complement component C5, while loss of cytotoxic sensitivity of mouse leukemia cells bearing thymus-leukemia (TL) antigens following in vitro incubation with TL antiserum (antigenic modulation) involves mouse complement component C3 together with microaggregation of TL antigen-antibody complexes on the cell surface. We propose to investigate the relationship between plasma-mediated cytodestruction and modulation of leukemia cells, to determine how cytodestruction may be maximized, and modulation minimized, for ultimate application to cancer therapy. The mechanism of plasma-mediated leukemia cell lysis operative at the cell surface is not known, and we plan to develop as in vitro system to investigate the precise manner in which complement participates in selective cytodestruction. At the same time, antigenic modulation in vivo will be studied to determine how tumor cells escape from immune destruction within the animal. The specific requirements for modulation will be ascertained by comparative studies of modulation of TL antigens and other cell surface receptors, both in vitro and in vivo.